Sleep deprivation has been linked to the development of hypertension in humans. Increases of sympathetic neural outflow have been suggested as a potential mechanism for sleep deprived hypertension, but direct evidence is lacking. A recent report suggests that the associations between sleep deprivation and hypertension are more prevalent in women compared to men. Pilot data in this proposal not only support this concept, but also suggest sympathetic neural traffic as a potential mechanistic link for sleep deprived hypertension in women. The broad objective of this proposal is to determine neural and cardiovascular responses to sleep deprivation in men and women, and determine if sex and female reproductive hormones influence these responses. The project includes four specific aims. Specific Aim #1 will determine the effect of 24 hours sleep deprivation on resting muscle sympathetic nerve activity (MSNA) and blood pressure in men and women. We hypothesize that sleep deprivation will increase resting blood pressure more dramatically in women, and that those increases will be associated with increases in resting MSNA. Specific Aim #2 will determine the effect of 24 hour sleep deprivation on sympathetic and cardiovagal baroreflex function in men and women. We hypothesize that sleep deprivation will induce a more dramatic resetting of the sympathetic and cardiovagal baroreflexes in women compared to men. Specific Aim #3 will determine the effect of 24 hours sleep deprivation on neural and cardiovascular responses to mental stress in men and women. We hypothesize that sleep deprivation will augment neural and cardiovascular responses to mental stress more dramatically in women compared to men. Specific Aim #4 will determine if hormonal fluctuations associated with the menstrual cycle influence sympathetic and cardiovascular responses to sleep deprivation in women. We hypothesize augmented sympathoexcitatory responses to sleep deprivation during the midluteal phase of the menstrual cycle. Two studies will be performed to address these specific aims. Study 1 will examine neural and cardiovascular responses to sleep deprivation in both men and women, while Study 2 will examine only women during the early follicular and midluteal phases of the menstrual cycle. Both studies will employ a randomized, crossover design. Microneurography will be used to provide direct recordings of sympathetic neural traffic, while Valsalva maneuvers and mental arithmetic will be utilized to assess sympathetic baroreflex function and mental stress responses. In summary, the associations between sleep deprivation and hypertension are poorly understood. The proposed research will advance our understanding of neural and cardiovascular responses to sleep deprivation, and has the potential to provide a mechanistic link between sleep deprivation and hypertension. PUBLIC HEALTH RELEVANCE: Sleep deprivation has been linked to hypertension, yet the mechanisms underlying this relationship remain unclear. This project will examine the effects of sleep deprivation on neural and cardiovascular control in men and women, providing new knowledge in the area of cardiovascular disease research.